Bio-reactor

Abstract

A bio-reactor for cultivating cells, comprising a culture vessel, at least one gas supply and/or liquid feed in addition to supply devices for gases and/or liquids enabling gases or liquids to be fed to the culture vessel. A mixer device, especially a Venturi nozzle is arranged between the supply device and gas supply or liquid feed in order to mix gas and/or liquid from the gas supply or liquid feed.

1 . A method for the dosed addition of one or several fluids or fluid mixtures to one or several culture vessels, characterized by the use of at least one carrier fluid, which is quantitatively, discontinuously taken through a clock valve from a pressurized storage vessel having a defined internal volume.  
     
     
         2 . A method according to  claim 1 , characterized by the use of a carrier gas or a carrier gas mixture.  
     
     
         3 . A method according to  claim 1  or  2 , characterized by the use of a carrier liquid or a carrier liquid mixture.  
     
     
         4 . A method according to  claim 1 , characterized by that the fluid(s) to be dosed are admixed to the carrier fluid(s) in a dosed manner through one or several Venturi nozzles.  
     
     
         5 . A method according to  claim 1  one of claims  1 , characterized by that the supply to the reaction medium in the culture vessel takes place through a Venturi nozzle for a better mixture.  
     
     
         6 . A method according to  claim 1 , characterized by that a filter or the like at the side inlet of the Venturi nozzle in the reaction medium prevents the ingress of microorganisms into the nozzle.  
     
     
         7 . A method according to  claim 1 , characterized by a supply line to a headspace of the culture vessel.  
     
     
         8 . A method according to  claim 1 , characterized by an atomization device such as e.g. an ejector nozzle at the entrance of a headspace of the culture vessel.  
     
     
         9 . A method according to  claim 1 , characterized by a commutation of the supply to the culture vessel from the supply to the reaction medium to the supply to a headspace of the culture vessel and vice versa.  
     
     
         10 . A method according to  claim 2 , characterized by that the carrier gas or the carrier gas mixture is taken from a gas container under overpressure.  
     
     
         11 . A method according to  claim 10 , characterized by that the pressure in the gas container during the process is increased again once or several times after one removal or several removals through a supply line.  
     
     
         12 . A method according to  claim 1  for the dosage of several fluids, characterized by that they are admixed to the carrier fluid through various Venturi nozzles in series or parallel connection, preferably parallel connection, at the same time or in any order.  
     
     
         13 . A device for dosing gases or liquids or mixtures thereof for use at culture vessels for biological and biochemical reactions, characterized by that the device comprises at least one gas supply module according to drawing 1 or a module driving pump according to drawing 2 for producing a carrier fluid, a Venturi nozzle with clock valve and liquid feed with a pressure compensation capillary, or a dosage feed for gases, and a supply line, which terminates in the reaction liquid or in a headspace of the culture vessel, and wherein the gas supply module or the driving pump module generates a flow of carrier fluid, continuously or discontinuously, through the supply line toward the culture vessel.  
     
     
         14 . A device according to  claim 13 , characterized by that the volume of the gas is between 1 and 40% of the volume of the culture vessel.  
     
     
         15 . A device according to  claim 13 , characterized by that the volume of the gas can be varied by a piston in the range of 0 to 100% of the total volume.  
     
     
         16 . A device according to  claim 13 , characterized by that the clock rate of the valve(s) can be adjusted to the “gas hold-up” of the gas bubbles in the culture vessel, preferably is identical thereto, and the amount of the passed-through gas is performed by adjusting the piston according to  claim 15 .  
     
     
         17 . A device according to  claim 13 , characterized by that at least 1 liquid supply module or gas supply module according to drawing 1 is installed between the three-way valve and the culture vessel.  
     
     
         18 . A device according to  claim 13 , characterized by that the liquid supply module is composed of at least one Venturi nozzle and a liquid container, and the pressure compensation can take place either through the pressure compensation capillary to the gas container or through a connection to the external atmosphere.  
     
     
         19 . A device according to  claim 13 , characterized by that the liquid feeds are installed in any position, suspended, standing, lying with regard to the device and always have an air space of at least 2% of the total volume, into which the pressure compensation can take place.  
     
     
         20 . A device according to  claim 13 , characterized by that the gas dosage feed is composed of at least one gas inlet, a three-way valve or 2 valves, a gas container with variable internal volume (analogous to  claim 15) , and a valve opening is connected to a side inlet of a Venturi nozzle.  
     
     
         21 . A device according to  claim 13 , characterized by that the dimensions of the components of the device and thus the properties according to the invention can be adjusted to culture vessels from 1 milliliter to 50 liters volume.  
     
     
         22 . A device according to  claim 13 , characterized by that by means of the device, in particular also according to  claim 8 , better mixtures and exchange rates with the reaction liquid are obtained, so that, depending from the kind of cultivation, shaking or stirring of the culture vessel is not necessary.  
     
     
         23 . A device according to  claim 13 , characterized by that the tendency to foam formation of the reaction liquid is reduced by the kind of the discontinuous aeration and the gas supply.  
     
     
         24 . A device according to  claim 13 , characterized by that by the combination gas/liquid dosage, whether in the reaction liquid or in the headspace of the culture vessel, a shorter mixing time with the reaction liquid is achieved, and thus concentration gradients (e.g. substrate) are minimized.  
     
     
         25 . A device according to  claim 13 , characterized by that in particular by the dosage into the headspace of the culture vessel, a more effective use of the properties of the dosed liquids takes place.  
     
     
         26 . A device according to  claim 13 , characterized by that by the use of the device, the consumption of anti-foam agents can be minimized.  
     
     
         27 . A device according to  claim 13 , characterized by that the thus dosed liquids or a combination of several of them can have an effect on the reaction liquid.  
     
     
         28 . A device according to  claim 13 , characterized by that the gases dosed are used for generating an artificial atmosphere in the headspace of the culture vessel.  
     
     
         29 . A device according to  claim 13 , characterized by that the device is only connected to a power supply and transport medium supply, and all measurement and control parameters are exchanged with the control EDP system via an infrared interface.  
     
     
         30 . A bio-reactor for the cultivation of cells, in particular according to the method of  claim 1 , comprising a culture vessel, one or several gas supplies and/or one or several liquid supplies as well as supply devices for gases and/or liquids, by means of which gases and/or liquids can be added to the culture vessel, wherein between the supply device and the gas supply or liquid supply, a mixing device, in particular a Venturi nozzle, for mixing gas and/or liquid from the gas supply or the liquid feed is installed.  
     
     
         31 . A bio-reactor according to  claim 30 , wherein gas and liquid are mixed to an aerosol.  
     
     
         32 . A bio-reactor according to  claim 30 , wherein between the mixing device and the gas supply or liquid feed, controllable valves, in particular clock valves, are installed.  
     
     
         33 . A method for operating a bio-reactor according to one of  claims 30  to  32 , wherein a gas or a liquid is used as a carrier fluid, wherein a gas or a liquid is admixed to the carrier fluid in the mixing device, and wherein the proportions of the mixed fluids are defined and are controlled or regulated.  
     
     
         34 . A method according to  claim 33 , wherein the mixed fluids are added in a defined mass flow to the culture vessel.